chr17-76737321-G-A

Variant names:

• chr17-76737321-G-A
• rs3744061
• NM_001195427.2:c.-161C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001195427.2(SRSF2):​c.-161C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 973,052 control chromosomes in the GnomAD database, including 138,841 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.42 (16105 hom., cov: 35)
  • Exomes 𝑓: 0.54 (122736 hom.)
• Consequence: SRSF2 NM_001195427.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26
• Publications: 32 publications found

Genes affected

SRSF2 (HGNC:10783): (serine and arginine rich splicing factor 2) The protein encoded by this gene is a member of the serine/arginine (SR)-rich family of pre-mRNA splicing factors, which constitute part of the spliceosome. Each of these factors contains an RNA recognition motif (RRM) for binding RNA and an RS domain for binding other proteins. The RS domain is rich in serine and arginine residues and facilitates interaction between different SR splicing factors. In addition to being critical for mRNA splicing, the SR proteins have also been shown to be involved in mRNA export from the nucleus and in translation. Two transcript variants encoding the same protein and one non-coding transcript variant have been found for this gene. In addition, a pseudogene of this gene has been found on chromosome 11. [provided by RefSeq, Sep 2010]

MFSD11 (HGNC:25458): (major facilitator superfamily domain containing 11) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000267168 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRSF2	NM_001195427.2	c.-161C>T		5_prime_UTR_variant	Exon 1 of 3	ENST00000359995.10	NP_001182356.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRSF2	ENST00000359995.10	c.-161C>T		5_prime_UTR_variant	Exon 1 of 3	1	NM_001195427.2	ENSP00000353089.5
ENSG00000267168	ENST00000587459.1	c.239-961G>A		intron_variant	Intron 1 of 1	5		ENSP00000466829.1

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63381 AN: 152060 Hom.: 16107 Cov.: 35

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.768

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.665

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.431

GnomAD4 exome AF: 0.538 AC: 441886 AN: 820874 Hom.: 122736 Cov.: 10 AF XY: 0.536 AC XY: 218436 AN XY: 407648

African (AFR) AF: 0.0924 AC: 1780 AN: 19264

American (AMR) AF: 0.444 AC: 8033 AN: 18086

Ashkenazi Jewish (ASJ) AF: 0.650 AC: 9922 AN: 15258

East Asian (EAS) AF: 0.498 AC: 15646 AN: 31434

South Asian (SAS) AF: 0.408 AC: 18986 AN: 46518

European-Finnish (FIN) AF: 0.482 AC: 14119 AN: 29268

Middle Eastern (MID) AF: 0.529 AC: 1395 AN: 2638

European-Non Finnish (NFE) AF: 0.568 AC: 352936 AN: 621096

Other (OTH) AF: 0.511 AC: 19069 AN: 37312

GnomAD4 genome AF: 0.416 AC: 63371 AN: 152178 Hom.: 16105 Cov.: 35 AF XY: 0.415 AC XY: 30830 AN XY: 74366

African (AFR) AF: 0.108 AC: 4473 AN: 41554

American (AMR) AF: 0.447 AC: 6842 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.665 AC: 2308 AN: 3472

East Asian (EAS) AF: 0.476 AC: 2451 AN: 5144

South Asian (SAS) AF: 0.415 AC: 2003 AN: 4830

European-Finnish (FIN) AF: 0.488 AC: 5168 AN: 10584

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.564 AC: 38357 AN: 67978

Other (OTH) AF: 0.434 AC: 916 AN: 2112

Alfa AF: 0.497 Hom.: 41904

Bravo AF: 0.402

Asia WGS AF: 0.407 AC: 1417 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.99
DANN	Benign	0.89
PhyloP100		-1.3
PromoterAI		0.18	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3744061; hg19: chr17-74733403;